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Background: The effect of dietary modifications on pain and joint function in adults with osteoarthritis (OA) is an emerging area of study. This systematic review aimed to evaluate if adults with OA who consume diets with a higher proportion of plant phenols and omega-3 fatty acids would have less pain and improved joint function than those with a higher proportion of saturated fatty acids, omega-6 fatty acids and refined carbohydrates., Methods: Database searches of CINAHL (EBSCO), Clinical Trials (NIH-NLM), Cochrane Library (Wiley), Dissertation & Thesis Global (ProQuest), Embase (Elsevier), Medline (OVID), PubMed (NLM), Scopus (Elsevier), Web of Sciences (Clarivate) for clinical trials identified 7763 articles published between January 2015 and May 2023. After an independent review of the articles, seven randomised clinical trials and one nonrandomised clinical trial were included in the analysis. Because of the heterogeneity of the outcome measures, a meta-analysis was not possible., Results: Participants who were instructed to consume high-phenol/high-omega-3 fatty acid diets reported significant improvements in pain and physical function scores. The greatest improvement was reported by those who consumed a diet that had the most omega-3 fatty acids., Conclusion: Because of the high risk of bias, the strength of the evidence is limited. However, there is evidence that counselling adults with OA to replace refined grains and processed foods with whole plant foods, fish and plant oils may have a favourable effect on pain and physical function. Routine follow-up care regarding these diet modifications may be necessary to ensure adherence to this therapy., (© 2024 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Objective: The primary objective of this study was to evaluate the effect of a low-carbohydrate diet (LCD) compared with a control diet on pain in female patients with lipedema. The secondary objectives were to compare the impact of the two diets on quality of life (QoL) and investigate potential associations of changes in pain with changes in body weight, body composition, and ketosis., Methods: Adult female patients with lipedema and obesity were randomized to either the LCD or control diet (energy prescription: 1200 kcal/day) for 8 weeks. Body weight and body composition, pain (Brief Pain Inventory measured pain), and QoL (RAND 36-Item Health Survey [RAND-36], Impact of Weight on Quality of Life [IWQOL]-Lite, and Lymphoedema Quality of Life [LYMQOL]) were measured at baseline and at postintervention., Results: A total of 70 female patients (age, mean [SD], 47 [11] years; BMI 37 [5] kg/m 2 ) were included. The LCD group had greater weight loss (-2.8 kg; 95% CI: -4.1 to -1.0; p < 0.001) and larger reduction in pain now (-1.1; 95% CI: -1.9 to -0.3; p = 0.009) compared with the control group. No association was found between changes in pain now and weight loss. Both groups experienced improvements in several QoL dimensions., Conclusions: Diet-induced weight loss in women with lipedema can improve QoL. An energy-restricted LCD seems to be superior to a standard control diet in reducing pain., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Nutrition can play a pivotal role in the management of pain associated with chronic rheumatic diseases. There is a growing body of research linking certain nutrients from the diet to inflammation. Certain nutrients have been shown to improve pain associated with inflammation. Furthermore, certain dietary patterns have been shown to improve pain across multiple rheumatic conditions. Finally, maintaining a low body mass is associated with improved pain associated with chronic rheumatic diseases., Competing Interests: Declaration of competing interest We have no disclosures relevant to this article to report., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain., Methods: In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months' dietary regimens., Results: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic ( p = 0.003) and diastolic ( p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet., Conclusions: Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.

Background: Pain is a frequent symptom of atopic dermatitis (AD)., Objectives: The aims of the study were to evaluate the effects of dupilumab on pain/discomfort in AD and to determine whether pain correlates with other outcomes., Methods: This was a post hoc analysis of 5 randomized, placebo-controlled clinical trials in which adults with chronic AD received placebo or dupilumab 300 mg every 2 weeks or once weekly with and without topical corticosteroids. Proportions of patients with no pain/discomfort on this dimension of the 5-dimension EuroQoL (EQ-5D) at week 16 (all trials) and week 52 (CHRONOS) were compared between placebo and dupilumab. Correlations were evaluated between pain/discomfort and signs and symptoms of AD., Results: Among 2632 evaluated patients, 72.9% to 83.1% reported at least moderate pain/discomfort at baseline. Higher proportions treated with dupilumab reported no pain/discomfort at week 16 relative to placebo; risk differences ranged from 22.3% (95% confidence interval = 11.5%-33.1%) to 42.2% (95% confidence interval = 26.6%-57.8%, all P ≤ 0.0001), with similar effects observed at week 52. Correlations at baseline of pain/discomfort with signs and symptoms of AD were low to moderate., Conclusions: Pain/discomfort, present in a substantial proportion of patients with moderate-to-severe AD, was significantly reduced by dupilumab treatment. Given the low-to-moderate correlations with other AD symptoms at baseline, pain likely represents a distinct AD symptom.Trial Registration: ClinicalTrials.gov identifiers NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Contact Dermatitis Society.)

Ketogenic diets are very low carbohydrate, high fat, moderate protein diets used to treat medication-resistant epilepsy. Growing evidence suggests that one of the ketogenic diet's main mechanisms of action is reducing inflammation. Here, we examined the diet's effects on experimental inflammatory pain in rodent models. Young adult rats and mice were placed on the ketogenic diet or maintained on control diet. After 3-4 weeks on their respective diets, complete Freund's adjuvant (CFA) was injected in one hindpaw to induce inflammation; the contralateral paw was used as the control. Tactile sensitivity (von Frey) and indicators of spontaneous pain were quantified before and after CFA injection. Ketogenic diet treatment significantly reduced tactile allodynia in both rats and mice, though with a species-specific time course. There was a strong trend to reduced spontaneous pain in rats but not mice. These data suggest that ketogenic diets or other ketogenic treatments might be useful treatments for conditions involving inflammatory pain.

Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named "non-neuronal cells." In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local " on demand " synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide-either by decreasing its degradation or exogenous administration-is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

Fibromyalgia syndrome (FMS) is characterised by chronic widespread pain alongside fatigue, poor sleep quality and numerous comorbidities. It is estimated to have a worldwide prevalence of 1.78%, with a predominance in females. Treatment interventions for fibromyalgia have limited success, leading to many patients seeking alternative forms of treatment, including modifications to their diet and lifestyle. The effectiveness of dietary changes in fibromyalgia has not been widely researched or evaluated. This systematic review identified twenty-two studies, including 18 randomised control trials (RCTs) and four cohort studies which were eligible for inclusion. In total these studies investigated 17 different nutritional interventions. Significant improvements in reported pain were observed for those following a vegan diet, as well as with the low fermentable oligo di-mono-saccharides and polyols (FODMAP) diets. Supplementation with Chlorella green algae, coenzyme Q10, acetyl-l-carnitine or a combination of vitamin C and E significantly improved measures of pain. Interpretation of these studies was limited due to the frequent poor quality of the study design, the wide heterogeneity between studies, the small sample size and a high degree of bias. Therefore, there is insufficient evidence to recommend any one particular nutritional intervention for the management of fibromyalgia and further research is needed.

The main causes of liver injury are associated with inflammation and permanent damage. They can cause chronic liver disease (CLD), which is mainly related to viral hepatitis, alcohol consumption and non-alcoholic steatohepatitis, leading to fibrosis, cirrhosis and hepatocellular carcinoma. These conditions prevent the liver from working normally and make it begin to fail, which in turn may prompt a liver transplant. CLD and cirrhosis are the eleventh cause of death worldwide. At present, there are no approved pharmacological treatments to prevent, treat or resolve liver fibrosis. The prevalence of pain in the hepatic disease is elevated with ranges between 30% and 40%. Most of the pain drugs require hepatic function; therefore, the suitable control of pain is still a clinical challenge. Specialized pro-resolving mediators (SPM): lipoxins, resolvins, protectins and maresins, are potent endogenous molecules (nM concentrations) that modulate inflammatory body responses by reducing neutrophil infiltration, macrophage activity and pain sensitization. SPM have anti-inflammatory properties, stimulate tissue resolution, repair and regeneration, and exhibit anti-nociceptive actions. Furthermore, SPM were tried on different cellular, animal models and human observational data of liver injury, improving the pathogenesis of inflammation and fibrosis. In the present work, we will describe recent evidence that suggests that SPM can be used as a therapeutic option for CLD. Additionally, we will examine the role of SPM in the control of pain in pathologies associated with liver injury., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Drug utilization reviews (DURs) can be used to promote rational prescribing and ensure compliance with standard treatment guidelines. In recent years, the use of tramadol hydrochloride (HCl) for pain has increased significantly across countries. We sought to determine prescribing patterns and the use of tramadol in a regional hospital in South Africa to provide future guidance in view of increasing concerns with the prescribing of tramadol., Method: A prospective, quantitative and descriptive study was conducted over two months. Outpatient and inpatient prescriptions and ward requisitions where tramadol HCl was prescribed or ordered were identified, which included outpatients collecting antiretroviral treatment. Prescriptions were reviewed and evaluated to determine the level of compliance to the Standard Treatment Guidelines and Essential Medicines List (STGs/EML) for South Africa as a measure of rational prescribing. Quantities issued to the inpatient wards and expenditure incurred by the pharmacy departments were assessed to determine overall usage and total costs., Results: In total, 415 tramadol HCl prescriptions were collected over a 2-month period. Compliance was 70.1% to the STGs/EML. The outpatient pharmacy department had the highest compliance at 76.4% while the antiretroviral pharmacy compliance was 29.1%. Most prescriptions dispensed at the outpatient pharmacy were from the Surgical Outpatient Department (140; 33.7%) and the Orthopedic Outpatient Department (108; 26.0%). The outpatient pharmacy had the highest tramadol HCl consumption and expenditure at $4,874.13 (R72,054.28), while the inpatient pharmacy's expenditure was $2,526.63 (R37,351.20), and the antiretroviral pharmacy $590.13 (R8,722.75). The hospital's tramadol HCl expenditure increased when compared to previous financial years, from $10,576.04 (R156,326.00) in 2014-2015 to $39,584.00 (R585,088.80) in 2016-2017., Conclusion: This study highlights the need for the implementation of monitoring and evaluation tools to enhance rational prescribing and use of tramadol HCl. These are being implemented and will be evaluated in future projects.

Osteoarthritis (OA) is a degenerative condition of joints, causing pain and swelling, and can be caused or worsened by trauma and obesity. The objectives of this study were to determine whether pain behaviour and progression of OA were increased in rats with trauma-induced OA fed dietary saturated fatty acids (SFA). Male Wistar rats were fed either a corn starch diet (C) or high-carbohydrate high-fat diet (H) with either 20% beef tallow or SFA (lauric (HLA), myristic (HMA), palmitic (HPA) or stearic (HSA) acids) for 16 weeks prior to and 8 weeks after excision of the medial meniscus of right knee joint to initiate OA when pain behaviour, glial activity, progression of knee OA, inflammatory mediators and signs of metabolic syndrome were assessed. Rats fed beef tallow, palmitic or stearic acids showed increased pain symptoms characterised by decreased hind paw/limb withdrawal thresholds and grip strengths and increased spinal astrogliosis and microgliosis compared to rats fed lauric or myristic acids. However, the severity of OA joint damage was unchanged by these dietary manipulations. We conclude that pain symptoms of trauma-induced OA in rats worsen with increased dietary beef tallow or palmitic or stearic acids, but improve with lauric or myristic acids, despite unchanged OA cartilage damage.

We herein report a 28-year-old woman with type 1 diabetes with an asymptomatic pontine lesion and diabetic amyotrophy. She had suffered from diabetes from 10 years old. Treatment in a hospital reduced the hemoglobin A1c level from 14.2% to 7.2% for approximately 2 months. She suffered from acute-onset pain and weakness of the lower limb muscles without central nervous system manifestations. Magnetic resonance imaging showed high-intensity lesions at the brainstem and lower limb muscles on T2-weighted images. These findings and symptoms gradually resolved. Rapid treatment of poor glycemic control might increase the risk of asymptomatic pontine lesions and diabetic amyotrophy.

Purpose: The aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or treatment. We recently reported increased serum levels of the proinflammatory molecules substance P (SP) and tumor necrosis factor (TNF) in patients with FMS as compared to those in normal controls., Methods: This prospective, open-label study was conducted in patients with FMS (n = 87; 80 women, 7 men; age range, 18-80 years) selected from 2 clinical centers in Spain. Patients were administered the supplement and were evaluated at weeks 1 (before treatment), 4, 8, and 12 (end of treatment) for clinical parameters of functioning, fatigue, and pain, as well as overall impression. Patients were directed to take 1 capsule per day in the morning for the first 4 weeks, followed by 1 capsule in the morning and 1 capsule in the evening for the remaining 8 weeks. Differences in symptom scores in patients with FMS between weeks 1 and weeks 4, 8, and 12 were evaluated using ANOVA. Blood was obtained and serum separated in patients with FMS at 1 and 12 weeks and in a separate population of healthy controls (n = 20; 15 women, 5 men; age range, 25-65 years). Serum levels of SP and TNF were measured in patients with FMS at 1 and 12 weeks and in healthy controls by ELISA. TNF and SP levels in patients with FMS were compared between weeks 1 and 12, as well as between patients with FMS and untreated controls, using the Mann-Whitney U test., Findings: Clinical parameters of functioning, fatigue, and pain, as well as overall impression, were improved significantly at 4 weeks as compared to 1 week and remained unchanged for the duration of the study (all, P < 0.0001). Serum TNF and SP levels were significantly elevated at 1 week in patients with FMS compared to controls and were decreased significantly at 12 weeks as compared to 1 week (all, P < 0.0001)., Implications: Our findings indicate that this dietary supplement may significantly improve symptoms in patients with FMS. This is the first time to our knowledge that any molecule has been reported to be associated with a reduction in serum SP level. Consequently, the supplement or its hypothesized main active ingredient, spermine, may be developed as a novel treatment approach to FMS or other neuroinflammatory conditions. ClinicalTrials.gov identifier: NCT03911882., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: It has been suggested that environmental and lifestyle factors might contribute to the severity and progression of inflammation in rheumatoid arthritis. An intervention generating high interest due to its supposed anti-inflammatory properties is the Mediterranean diet., Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach., Results and Conclusions: We identified seven systematic reviews including four primary studies, of which only one corresponded to a randomized trial. We concluded Mediterranean diet may make little or no difference in pain or disease activity and may slightly increase weight in rheumatoid arthritis patients, but the certainty of the evidence is low. On the other hand, it was not possible to clearly establish whether Mediterranean diet has any effect on functionality, morning stiffness or quality of life as the certainty of the existing evidence has been assessed as very low.

Introduction: Knee osteoarthritis is a highly prevalent chronic disease, associated with various risk factors and with multiple treatment options. Overweight is among the main risk factors and also constitutes an aggravating factor of the symptoms. It has been suggested that weight loss would be able to improve symptoms and to stop the progression. It can be achieved by several methods: exercise, diet, drugs, surgery, or a combination of them. Apparently, diet is a reasonable option given its availability, low technical complexity and greater acceptability, especially in the population susceptible to developing knee osteoarthritis, but it is not clear whether the benefit of diet as the only intervention leads to symptomatic improvement., Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach., Results and Conclusions: We identified seven systematic reviews including six primary studies overall, all corresponding to randomized trials. We concluded diet may improve functionality and quality of life, with probably minimal or no adverse effects. However, we are uncertain whether diet reduces pain as the certainty of the evidence has been assessed as very low.

Osteoarthritis (OA) is the most common joint disorder in the world and is the most frequent cause of walking related disability among older adults in the US, which brings a significant economic burden and reduces quality of life. The initiation and development of OA typically involves degeneration or progressive loss of the structure and function of articular cartilage. Inflammation is one of the major drives of the progression of OA. Dietary polyphenols have been studied for their anti-inflammatory properties and potential anabolic effects on the cartilage cells. Blueberries are widely consumed and are high in dietary polyphenols, therefore regular consumption of blueberries may help improve OA. The purpose of the present study was to examine the effect of freeze dried whole blueberries on pain, gait performance, and inflammation in individuals with symptomatic knee OA. In a randomized, double-blind trial, adults age 45 to 79 with symptomatic knee OA, were randomized to either consume 40 g freeze-dried blueberry powder ( n = 33) or placebo powder ( n = 30) daily for four months. Blood draws and assessment of pain and gait were conducted at baseline, two months, and four months. Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaires were used to assess pain and GAITRite ® electronic walkway was used to evaluate gait spatiotemporal parameters. WOMAC total score and sub-groups, including pain, stiffness, and difficulty to perform daily activities decreased significantly in the blueberry treatment group ( p < 0.05), but improvement of WOMAC total score and difficulty to perform daily activities were not observed in the placebo group. Normal walking pace single support percentage for both limbs increased ( p = or < 0.007), while double support percentage for both limbs decreased in the blueberry treatment group ( p = or < 0.003). No significant changes were observed in plasma concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10, IL-13, matrix metalloproteinases (MMP)-3, MMP-13, and monocyte chemoattractant protein-1 (MCP-1) in both treatment groups. However, an increasing trend for IL-13 concentration and a decreasing trend in MCP-1 concentration were noted in the blueberry group. The findings of this study suggest that daily incorporation of whole blueberries may reduce pain, stiffness, and difficulty to perform daily activities, while improving gait performance, and would therefore improve quality of life in individuals with symptomatic knee OA.

The aim of this study was to examine the effect of a six-week 2 × 2 design on pain scores, quality of life, and dietary intake in patients attending an Australian tertiary pain clinic. The two intervention components were (1) personalized dietary consultations or waitlist control, and (2) active or placebo dietary supplement (fruit juice). Sixty participants were randomized into one of four groups at baseline (68% female, mean age 49 ± 15 years) with 42 completing the study (70% retention). All groups had statistically significant improvements in three of five pain outcomes. The personalized dietary consultation groups had clinically important improvements in three of five pain outcomes compared to the waitlist control groups. All groups had a statistically significant improvement in six of eight quality-of-life categories post intervention. All groups increased percentage energy from nutrient-dense foods (+5.2 ± 1.4%, p < 0.001) with a significant group-by-time effect for percentage energy from total fat ( p = 0.024), with the personalized dietary consultations plus placebo fruit juice reporting the largest reduction (-5.7 ± 2.3%). This study indicates that dietitian-delivered dietary intervention can improve pain scores, quality of life, and dietary intake of people experiencing chronic pain. Future research should evaluate efficacy in a full-powered randomized control trial.

Background and Aim: Peripheral neuropathy is a common extraintestinal manifestation of gluten sensitivity (gluten neuropathy). We aimed to establish the prevalence of neuropathic pain in patients with otherwise idiopathic PN and gluten sensitivity (positive antigliadin, endomysial, and/or transglutaminase antibodies, with or without enteropathy) and to describe any contributory factors., Methods: All consecutive patients with gluten neuropathy (GN) attending a specialist gluten/neurology clinic were invited to participate. Pain was assessed via the DN4 questionnaire and the visual analog scale. Overall Neuropathy Limitations Scale was used to assess the severity of neuropathy. The Mental Health Index (MHI-5) was used to measure participants' general mental health status., Results: In total, 60 patients (76.7% males, mean age 69.9 ± 10.1 years) with GN were recruited. Neuropathic pain was present in 33 patients (55.0%). Comparison between groups of painful and not painful GN did not show significant differences regarding age, gender, neuropathy severity and neuropathy type. Patients with painless GN were more likely to be on a strict gluten-free diet (55.6 versus 21.2%, p = 0.006). Patients with painful GN presented with significantly worse MHI-5 score (75.9 ± 13.8 versus 87.4 ± 8.1, p < 0.001). Multivariate analysis showed that, after adjusting for age, gender and MHI-5, strict gluten-free diet was associated with lowering the odds of peripheral neuropathic pain by 88.7% (95% CI 47.2-97.6%, p = 0.006)., Conclusion: Neuropathic pain is very prevalent in GN and is associated with poorer mental health status. Strict gluten-free diet might be protective as it is associated with a significant reduction of the odds of peripheral neuropathic pain associated to GN.

Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current therapies lack. Nutraceuticals refer to compounds or materials that can function as nutrition and exert a potential therapeutic effect, including the relief of pain, such as pain related to arthritis, of which osteoarthritis (OA) is the most common form. Of interest, nutraceuticals have recently been shown to have potential in relieving OA pain in human clinical trials. Emerging evidence indicates nutraceuticals may represent promising alternatives for the relief of OA pain. In this paper, we will overview OA pain and the use of nutraceuticals in OA pain management, focusing on those that have been evaluated by clinical trials. Furthermore, we discuss the biologic and pharmacologic actions underlying the nutraceutical effects on pain relief based on the potential active ingredients identified from traditional nutraceuticals in OA pain management and their potential for drug development. The review concludes by sharing our viewpoints that future studies should prioritize elucidating the mechanisms of action of nutraceuticals in OA and developing nutraceuticals that not only relieve OA pain, but also mitigate OA pathology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Observational studies suggest that vitamin D deficiency is associated with higher risk of pain. However, evidence on the effect of vitamin D supplementation on pain is limited and contradictory. The aim of this study was to compare the effect of monthly high-dose vitamin D supplementation on a pain impact questionnaire (PIQ-6) score and prescription of analgesics in the general population. We performed a randomized, double-blind, placebo-controlled trial of 5108 community-dwelling participants, aged 50 to 84 years, who were randomly assigned to receive monthly 100,000-IU capsules of vitamin D3 (n = 2558) or placebo (n = 2550) for a median of 3.3 years. The PIQ-6 was administered at baseline, year 1, and final follow-up. Analgesic prescription data were collected from Ministry of Health. There was no difference in mean PIQ-6 score at the end of follow-up (adjusted mean difference: 0.06; P = 0.82) between the vitamin D (n = 2041) and placebo (n = 2014) participants. The proportion of participants dispensed one or more opioids was similar in the vitamin D group (n = 559, 21.9%) compared with placebo (n = 593, 23.3%); the relative risk (RR) adjusted for age, sex, and ethnicity was 0.94 (P = 0.24). Similar results were observed for dispensing of nonsteroidal anti-inflammatory drugs (RR = 0.94; P = 0.24) and other nonopioids (RR = 0.98; P = 0.34). Focusing on vitamin D deficient participants (<50 nmol/L, 24.9%), there was a lower risk of dispensing nonsteroidal anti-inflammatory drugs in the vitamin D group compared with placebo (RR = 0.87; P = 0.009); all other subgroup analyses were not significant. Long-term monthly high-dose vitamin D supplementation did not improve mean PIQ-6 score or reduce analgesic dispensing in the general population.

In recent years, interest in the relationship between gut microbiota and disease states has grown considerably. Indeed, several strategies have been employed to modify the microbiome through the administration of different diets, by the administration of antibiotics or probiotics, or even by transplantation of feces. In the present manuscript, we focus specifically on the potential application of probiotics, which seem to be a safe strategy, in the management of digestive, pain, and emotional disorders. We present evidence from animal models and human studies, notwithstanding that translation to clinic still deserves further investigation. The microbiome influences gut functions as well as neurological activity by a variety of mechanisms, which are also discussed. The design and performance of larger trials is urgently needed to verify whether these new strategies might be useful not only for the treatment of disorders affecting the gastrointestinal tract but also in the management of emotional and pain disorders not directly related to the gut.

Competing Interests: There are no conflicts of interest.

Background: fibromyalgia is a disease of unknown origin characterized by chronic muscular pain. The lack of knowledge about this disease is one of the main causes that makes complex to make a diagnosis and an appropriate treatment., Objective: the main objective of this study was to know the efficacy of a physiotherapy treatment combined with a lacto-vegetarian dietary-nutritional intervention, on low back pain and body composition in women with fibromyalgia., Methods: twenty-one women were randomly divided into three groups: A (core stabilization exercises + lacto-vegetarian diet), B (placebo + lacto-vegetarian diet) and C (control). The intervention lasted 4 weeks. Pain assessments (EVA scale) and body composition (bioimpedance) were performed at the beginning and at the end of the intervention., Results: group A showed significant changes in pain reduction and body composition at the end of the intervention, increasing muscle mass and decreasing fat mass. In addition, this group significantly improved outcomes compared to groups B and C. The correlations showed a relationship between muscle mass and pain reduction referred to at the end of the study in patients in group A., Conclusions: four-week intervention program combining core stabilization exercises plus lacto-vegetarian diet in patients with fibromyalgia who have low back pain contributes to pain reduction and improved body composition.

Background: This double-blind randomized controlled experimental study aimed to determine the effects of breast milk and sucrose in reducing pain in preterm infants during retinopathy of prematurity (ROP) examination., Materials and Methods: This study was conducted with 60 preterm infants (breast milk group = 20, sucrose group = 20, and control/distilled water group = 20) meeting the inclusion criteria. The data were collected with the use of an Infant Evaluation Form, Procedure Monitoring Form, and Premature Infant Pain Profile (PIPP). The preterm infants were provided with 1 mL of breast milk, sucrose, and distilled water before the ROP examination. The pain level in preterm infants was measured by the PIPP 5 minutes before, during, and 5 minutes after the ROP examination. The ROP examinations were video recorded, and videos were evaluated by three observers blinded to the study., Results: No significant difference was determined between the three groups in terms of their postconceptional and postnatal ages, their body weights at birth and during the ROP examination. The PIPP scores of the preterm infants in the three groups were higher during the ROP examination and were not significantly different. The PIPP scores of the control group were significantly higher than those in the breast milk and sucrose groups after the ROP examination (p < 0.001). The preterm infants in the breast milk group recovered and returned to their initial values more quickly after the ROP examination than the infants in the sucrose group., Conclusion: To reduce pain in preterm infants during ROP examination, breast milk is recommended.

Background: Two studies have demonstrated an analgesic effect of maternal milk odor in preterm neonates, without specifying the method of olfactory stimulation. Research aim: This study aimed to assess the analgesic effect of maternal milk odor in preterm neonates by using a standardized method of olfactory stimulation., Methods: This trial was prospective, randomized, controlled, double blinded, and centrally administered. The inclusion criteria for breastfed infants included being born between 30 and 36 weeks + 6 days gestational age and being less than 10 days postnatal age. There were two groups: (a) A maternal milk odor group underwent a venipuncture with a diffuser emitting their own mother's milk odor and (2) a control group underwent a venipuncture with an odorless diffuser. The primary outcome was the Premature Infant Pain Profile (PIPP) score, with secondary outcomes being the French scale of neonatal pain-Douleur Aiguë du Nouveau-né (DAN) scale-and crying duration. All neonates were given a dummy., Results: Our study included 16 neonates in the maternal milk odor group and 17 in the control group. Neonates exposed to their own mother's milk odor had a significantly lower median PIPP score during venipuncture compared with the control group (6.3 [interquartile range (IQR) = 5-10] versus 12.0 [IQR = 7-13], p = .03). There was no significant difference between the DAN scores in the two groups ( p = .06). Maternal milk odor significantly reduced crying duration after venipuncture (0 [IQR = 0-0] versus 0 [IQR = 0-18], p = .04)., Conclusion: Maternal milk odor has an analgesic effect on preterm neonates.

Background: Polyamines have been identified as pain agonists and interact with N-methyl-D-aspartate receptors. A prospective, randomized, multicenter, and blinded phase II clinical trial was conducted to evaluate a polyamine-deficient diet for the treatment of perioperative pain in patients during spinal surgery., Methods: All analyses followed the intention-to-treat principle. The trial was designed to evaluate the dose-ranging effect of a low polyamine diet with respect to a total (group 1) or partial (group 2) polyamine diet on perioperative pain (7 d before and 5 d after surgery). Pain (numerical scale at rest and motion), quality of life questionnaires (Brief Pain Inventory, EIFEL questionnaire, and Short Form-12 acute questionnaire), and tolerance of and compliance with the nutritional program were measured., Results: Compliance (preoperatively: 100% in group 1 and 83% in group 2; postoperatively: 83% in group 1 and 71% in group 2) and tolerance were good. After 7 d following the diet before surgery, decreased pain was observed in group 1 whereas no effect was observed in group 2 (P = 0.144). This analgesic effect became significant in group 1 in the subgroup of patients with initial high levels of pain (NS ≥ 4) at rest (P = 0.03) and during motion (P = 0.011). Quality of life was significantly improved in group 1 (P = 0.0465). In the postoperative period, pain was significantly decreased in group 1 compared to group 2 at rest (P = 0.022) and during motion (P = 0.029). The effect was significantly better on patients with higher initial pain both at rest (P = 0.013) and during motion (P = 0.005) in group 1 compared to group 2., Conclusion: Suppression of polyamines from the diet offers a nutrition-based treatment option for perioperative pain reduction independent of and complementary to typical analgesic approaches., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Dietary supplementation with methyl donors can influence the programming of epigenetic patterns resulting in persistent alterations in disease susceptibility and behavior. However, the dietary effects of methyl donors on pain have not been explored. In this study, we evaluated the effects of dietary methyl donor content on pain responses in mice., Methods: Male and female C57BL/6J mice were treated with high or low methyl donor diets either in the perinatal period or after weaning. Mechanical and thermal nociceptive sensitivity were measured before and after incision., Results: Mice fed high or low methyl donor diets displayed equal weight gain over the course of the experiments. When exposed to these dietary manipulations in the perinatal period, only male offspring of dams fed a high methyl donor diet displayed increased mechanical allodynia. Hindpaw incision in these animals caused enhanced nociceptive sensitization, but dietary history did not affect the duration of sensitization. For mice exposed to high or low methyl donor diets after weaning, no significant differences were observed in mechanical or thermal nociceptive sensitivity either at baseline or in response to hindpaw incision., Conclusions: Perinatal dietary factors such as methyl donor content may impact pain experiences in later life. These effects, however, may be specific to sex and pain modality.

Ketogenic diets are well established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain.

Pain in advanced cancer can have many causes, and they are not necessarily associated with the presence of cancer. Invalid daily food rations in terms of energy, nutritional value, and cooking techniques used can significantly impair quality of life, increase patients' pain and other somatic symptoms and aggravate malnutrition and cachexia. Basic dietary factors affecting the quality of life and severity of somatic symptoms are the nutritional value of the diet, the frequency of meals and their consistency, the presence of fiber, fat, sugars, lactose, gluten and nutraceuticals. Extremely important is the role of a team of specialists, that offers professional nutritional advice to the patients and their carers.

Objectives: To examine the effects of a challenge with monosodium glutamate (MSG) as compared to placebo on the symptoms of fibromyalgia (FM), in participants who initially experienced >30% remission of symptoms on an excitotoxin elimination diet., Methods: Fifty-seven FM patients who also had irritable bowel syndrome (IBS) were placed on a 4-week diet that excluded dietary additive excitotoxins including MSG and aspartame. Thirty-seven people completed the diet and 84% of those reported that >30% of their symptoms resolved, thus making them eligible to proceed to challenges. Subjects who improved on the diet were then randomised to a 2-week double-blind placebo-controlled crossover challenge with MSG or placebo for 3 consecutive days each week. The primary outcome measure was total symptom score. Secondary outcome measures included visual analogue pain scales (VAS for FM and IBS), an IBS Quality of Life Questionnaire (IBS QOL) and the Fibromyalgia Impact Questionnaire-Revised (FIQR). Repeated measures ANOVA was used to analyse crossover challenge results., Results: The MSG challenge, as compared to placebo, resulted in a significant return of symptoms (total symptom score, p<0.02); a worsening of fibromyalgia severity as determined by the FIQR (p<0.03); decreased quality of life in regards to IBS symptoms (IBS QOL, p<0.05); and a non-significant trend toward worsening FM pain based on visual analogue scale (VAS, p<0.07)., Conclusions: These findings suggest that dietary glutamate may be contributing to FM symptoms in some patients. Future research on the role of dietary excitotoxins in FM is warranted.

Background: The conceptual validity of kinetic gait analysis and disability outcome assessment methods has guided their use in the assessment of pain caused by osteoarthritis (OA). No consensus on the best clinical methods for pain evaluation in canine OA exists, particularly, when evaluating treatments where a smaller treatment effect is anticipated than with pharmacological pain killers. This study thus aimed at determining the technical validity of some clinical endpoints on OA pain in dogs using the green-lipped mussel (GLM)-enriched diet.Twenty-three adult dogs with clinical OA completed the prospective controlled study. All the dogs were fed a balanced diet over a 30-day control period followed by a GLM-enriched diet over a 60-day period. The kinetic gait analysis parameter (PVF(BW), peak vertical force adjusted for body weight change), electrodermal activity (EDA), and a standardized multifactorial pain questionnaire (MFQ) were performed on day (D) 0 (inclusion), D30 (start) and D90 (end). The owners completed a client-specific outcome measures (CSOM) instrument twice a week. Motor activity (MA) was continuously recorded in seven dogs using telemetered accelerometric counts. We hypothesized that these methods would produce convergent results related to diet changes. A Type I error of 0.05 was adjusted to correct for the multiplicity of the primary clinical endpoints., Results: Neither the EDA nor the MFQ were found reliable or could be validated. Changes in the PVFBW (P(adj) = 0.0004), the CSOM (P(adj) = 0.006) and the MA intensity (P(adj) = 0.02) from D0 to D90 suggested an effect of diet(s). Only the PVFBW clearly increased after the GLM-diet (P(adj) = 0.003). The CSOM exhibited a negative relationship with the PVF(BW) (P = 0.02) and MA duration (P = 0.02)., Conclusions: The PVF(BW) exhibited the best technical validity for the characterization of the beneficial effect of a GLM-enriched diet. The CSOM and MA appeared less responsive following a GLM-diet, but these measures appeared complementary to gait analysis. Apparently, the CSOM provides the capacity to rely on pain OA assessment influenced by both lameness quantification (PVF(BW)) and physical functioning (MA).

Purpose of Review: Although many publications have documented the use of complementary and alternative medicine (CAM) in children and adolescents, most have lacked the scientific rigor to establish clear benefits over so-called conventional medicine. We reviewed the literature published in the past year to identify the types of CAM most often studied in children, the variety of conditions to which these modalities are applied, and the methodologies used in the articles exploring the most prevalent CAM modalities., Recent Findings: We identified 111 published articles on CAM use in children in 2011. The most common modalities were herbal/dietary supplements, acupuncture, massage, chiropractic, and homeopathy. The most commonly studied conditions were pain, headache, attention deficit hyperactivity disorder (ADHD), asthma, and colic. Although a majority of the articles consisted of reviews, case reports, and other nonhypothesis-driven methodologies, we did find that several were randomized controlled trials, meta-analyses, or systematic reviews. These methodologies, however, rarely accounted for the majority of publications on a particular therapy or condition., Summary: The use of CAM in children continues to occupy a niche area of interest for many providers and families, but only a minority of articles published in the past year utilized methods of sufficient rigor to provide a useful comparison to more conventional therapies.

Purpose of Review: This article reviews the current status of the definition of cancer cachexia, and comments on future initiatives to refine it and to use it as a foundation for a cancer cachexia classification system., Recent Findings: There has been a plethora of work by expert panels defining cachexia. Stemming from this work, an expert panel has published a definition of cancer cachexia and a three level staging system: precachexia, cachexia, and refractory cachexia. Colleagues in the cancer pain field have put forward a sophisticated pain classification system. Work to develop a similar classification system for cachexia is now commencing. Aside from improved communication, these efforts may also enable the oncology community to better appreciate the importance of cancer cachexia and to participate in interdisciplinary treatment programmes to combat cachexia., Summary: The quest to determine the pathophysiology of cancer cachexia and to use this knowledge to identify patient subsets will further research. Equally important, the fruits of this endeavour will lead to a higher priority for addressing cachexia with consequent development of a multimodal approach to management.

Dietary interventions involving antioxidants are of interest for reducing inflammation, improving joint motion, and altering pain perception. We evaluated the effect of oral consumption of a fruit and berry blend on pain and range of motion (ROM). This open-label clinical pilot study involved 14 study participants with limitations in ROM that was associated with pain and affected daily living. Participants included but were not limited to those with age-related osteoarthritis. Study participants consumed 120 mL MonaVie Active® fruit juice, predominantly containing açai pulp (Euterpe oleracea Mart.) and other fruit concentrates, daily for 12 weeks. Study participants were assessed at baseline and 2, 4, 8, and 12 weeks by structured nurse interviews, pain and activities of daily living (ADL) questionnaires, blood samples, and ROM assessment. Pain was scored by using a visual analogue scale. ROM was assessed by using dual digital inclinometry as recommended by American Medical Association guidelines. Consumption of the juice resulted in significant pain reduction, improved ROM measures, and improvement in ADLs. Serum antioxidant status, as monitored by the cell-based antioxidant protection in erythrocytes (CAP-e) assay, was improved within 2 weeks and continued to improve throughout the 12 weeks of study participation (P<.01). The inflammatory marker C-reactive protein was reduced at 12 weeks, but this change did not reach statistical significance. Lipid peroxidation decreased mildly at 12 weeks. The antioxidant status, as measured by the CAP-e bioassay, showed the best correlation with improvements in physical well-being (pain, ROM, and ADL). The significant association among increased antioxidant status, improved ROM, and pain reduction warrants further study.

Pain is brought into play by a system which detects and transmits messages signaling pain. Opioids negatively modulate nociception, but paradoxically also contribute to hyperalgesia. A nutritional approach with low polyamine contents helps to reduce this phenomenon without the harmful side effects of antihyperalgesic drugs.

Fish oil has been used to alleviate pain associated with inflammatory conditions such as rheumatoid arthritis. The anti-inflammatory property of fish oil is attributed to the n-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid. Contrarily, vegetable oils such as safflower oil are rich in n-6 fatty acids which are considered to be mediators of inflammation. This study investigates the effect of n-3 and n-6 fatty acids rich oils as dietary supplements on the thermally induced pain sensitivity in healthy mice. C57Bl/6J mice were fed diet containing regular fish oil, concentrated fish oil formulation (CFO) and safflower oil (SO) for 6 months. Pain sensitivity was measured by Plantar test and was correlated to the expression of acid sensing ion channels (ASICs), transient receptor potential vanilloid 1 (TRPV1) and c-fos in dorsal root ganglion cells. Significant delay in sensitivity to thermal nociception was observed in mice fed CFO compared to mice fed SO (p<0.05). A significant diminution in expression of ion channels such as ASIC1a (64%), ASIC13 (37%) and TRPV1 (56%) coupled with reduced expression of c-fos, a marker of neuronal activation, was observed in the dorsal root ganglion cells of mice fed CFO compared to that fed SO. In conclusion, we describe here the potential of fish oil supplement in reducing sensitivity to thermal nociception in normal mice., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Fatty acids, which are the essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a range of biological phenomena. Recently, an increasing number of physiologic and pharmacologic reports on fatty acids have improved our understanding of the association of fatty acids with certain diseases. It has also become apparent that functional properties of fatty acids are modulated by factors such as the amount of individual fatty acid intake and their distribution among organs. Recently, the functional relationship between polyunsaturated fatty acids and pain has been the focus of many studies. Both basic and clinical studies have shown that a dietary intake of n-3 series polyunsaturated fatty acids results in a reduction in the pain associated with rheumatoid arthritis, dysmenorrhea, inflammatory bowl disease, and neuropathy. In addition, levels of n-6 series polyunsaturated fatty acids are high in patients with chronic pain. These results indicate that polyunsaturated fatty acids play a vital role in pain regulation. In this review, we summarize a number of basic and clinical studies on polyunsaturated fatty acids and their association with pain.

Attention deficit/hyperactivity disorder (ADHD), a common behavioural disorder in children, may be associated with comorbid physical and sleep complaints. Dietary intervention studies have shown convincing evidence of efficacy in reducing ADHD symptoms in children. In this pilot study, we investigated the effects of an elimination diet on physical and sleep complaints in children with ADHD. A group of 27 children (3.8-8.5 years old), who all met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD, were assigned randomly to either a diet group (15/27) or a control group (12/27). The diet group followed a 5-week elimination diet; the control group adhered to their normal diet. Parents of both groups had to keep an extended diary and had to monitor the behaviour and the physical and sleep complaints of their child conscientiously. The primary endpoint was the clinical response, i.e. a decrease of physical and sleep complaints, at the end of the trial, based on parent ratings on a Physical Complaints Questionnaire. The number of physical and sleep complaints was significantly decreased in the diet group compared to the control group (p < 0.001), with a reduction in the diet group of 77% (p < 0.001, effect size = 2.0) and in the control group of 17% (p = 0.08, effect size = 0.2). Specific complaints that were significantly reduced were in three domains: headaches or bellyaches, unusual thirst or unusual perspiration, and sleep complaints. The reduction of complaints seemed to occur independently of the behavioural changes (p = 0.1). However, the power of this comparison was low. A positive correlation existed between the reduction of physical and behavioural symptoms (p < 0.01). The reduction did not differ between children with or without an atopic constitution (p = 0.7). An elimination diet may be an effective instrument to reduce physical complaints in children with ADHD, but more research is needed to determine the effects of food on (functional) somatic symptoms in children with and without ADHD. This trial was registered as an International Standard Randomised Controlled Trial, ISRCTN47247160.

Background: Reducing polyamine uptake by selecting low polyamine-containing foodstuffs and reducing bacterial gut production can improve performance status and pain control in hormone refractory prostate cancer (HRPC) patients. Long term PRD observance and tolerance were assessed. Cancer specific survival was studied in function of PRD and time of PRD initiation., Methods: Twenty-six volunteers, age: 68+/-10 years with metastatic HRPC accepted a polyamine reduced diet and partial gut decontamination with oral neomycin or nifuroxazide (750 mg daily, one week out of two). Time from HRPC to PRD initiation was 10+/-8 months. WHO performance status, EORTC pain scale, body weight, blood counts and serum proteins were regularly assessed. Sixteen other HRPC patients eating a normal diet served as "controls"., Results: Mean diet observance is 25+/-24 months. Tolerance is good. WHO performance status and EORTC pain scales were significantly improved respectively at 3 months (0.5+/-0.7 vs 0.7+/-0.9: p=0.03) and 6 months (0.5+/-0.8 vs 1+/-1.3, p=0.02) compared to initial values. Median cancer specific survival times after HRPC and PRD initiation are respectively 36 and 21 months. Eleven PRD patients started the diet before a 9 months cut-off period (after HRPC) and 15 patients after. Median cancer specific survival times for these two groups of patients are respectively 44 and 34 months, p=0.014. Median cancer specific survival times (after HRPC) for PRD patients compared to controls are 36 vs 17 months (p=0.004)., Conclusions: Polyamine-reduced diet is well observed and tolerated. It seems to improve and/or maintain quality of life for HRPC patients. Early PRD initiation in HRPC is promising and may impact favorably cancer specific survival. These results open a rationale for PRD in HRPC management and warrant further investigation., (2010 Elsevier Masson SAS. All rights reserved.)

The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain and inflammation directly, we fed juvenile and adult rats a control diet (standard rodent chow) or ketogenic diet (79% fat) ad libitum for 3-4 weeks. We then quantified hindpaw thermal nociception as a pain measure and complete Freund's adjuvant-induced local hindpaw swelling and plasma extravasation (fluid movement from the vasculature) as inflammation measures. Independent of age, maintenance on a ketogenic diet reduced the peripheral inflammatory response significantly as measured by paw swelling and plasma extravasation. The ketogenic diet also induced significant thermal hypoalgesia independent of age, shown by increased hindpaw withdrawal latency in the hotplate nociception test. Anti-inflammatory and hypoalgesic diet effects were generally more robust in juveniles. The ketogenic diet elevated plasma ketones similarly in both age groups, but caused slowed body growth only in juveniles. These data suggest that applying a ketogenic diet or exploiting cellular mechanisms associated with ketone-based metabolism offers new therapeutic opportunities for controlling pain and peripheral inflammation, and that such a metabolic strategy may offer significant benefits for children and adults.

Background: The present study aimed to directly assess and compare the usage, benefits and side-effects of dietary-related complementary and alternative medicine (CAM) use among adult cancer patients and non-cancer adults in Norwich, UK., Methods: Self-administered questionnaires were completed by 98 cancer patients and 92 non-cancer adults to compare demographics, types of CAM usage with reasons, benefits, side-effects and CAM information sources. The groups were matched for gender, age, marital status, education and household income. The mean ages were 62.7 and 59.7 years, respectively, with slightly more female than male participants., Results: CAM use was high in both groups (47% in cancer and 53% in non-cancer respondents, P > 0.05). The most widely-used diet-related CAM among both groups was the large intake of fruit, vegetables and juice, multivitamins, fish oils and glucosamine. Fish oil intake was significantly higher in the non-cancer group (P < 0.05), whereas selenium and beta-carotene supplements were significantly higher in the cancer group (P < 0.01 and P = 0.02, respectively). The main reasons for using CAM were to boost the immune system and to improve quality of life (P > 0.05). Reported benefits included increased optimism and hope for the cancer group and increased optimism and pain relief for the non-cancer group., Conclusions: Diet-related CAM is used frequently by both cancer patients and non-cancer adults, with many reported benefits and few reported side-effects. Significant differences between the groups included a higher prevalence of fish oil used by the non-cancer group, and a higher use of selenium and beta-carotene supplements in the cancer group.

Objective: To clarify the effect of Pycnogenol (Horphag Research, Geneva, Switzerland), French maritime pine bark extract, on endometriosis., Study Design: Fifty-eight women were included in this study. They were operated on conservatively for endometriosis and surgically diagnosed with the condition. All patients were followed at 4, 12, 24 and 48 weeks after starting treatment to check for endometriosis signs and symptoms, including changes in CA-125 and estrogen levels (E2). Thirty-two patients in the Pycnogenol treatment group took 60 mg Pycnogenol orally a day for 48 weeks. The 26 patients who received gonadotropin-releasing hormone agonist (Gn-RHa) were treated in the standard way., Results: Treatment with Pycnogenol slowly but steadily reduced the symptom scores. Treatment with Gn-RHa reduced the scores more efficiently; however, 24 weeks after the end of treatment, the scores suggested a recurrence of signs. No influence of treatment on menstrual cycles or E2 was observed in the Pycnogenol group. CA-125 decreased in both treatment groups. Patients with smaller endometriomas responded better to treatment as compared to patients with larger endometriomas. In the Gn-RHa group, the lowering of CA-125 concentrations was far more pronounced; however, a clear rebound effect was observed., Conclusion: Pycnogenol is a therapeutic alternative to Gn-RHa in the treatment of endometriosis.

Background: Pain associated with diabetic peripheral neuropathy (DPN) has a substantial negative impact on patients' quality of life., Objectives: The primary objective of this study was to evaluate the tolerability of capsules containing dextromethorphan (DM) and quinidine (Q) in patients with painful DPN. A secondary objective was to perform a preliminary assessment of the efficacy of DM/Q in this patient population., Methods: This was a multicenter, open-label, dose-escalation study. Eligible patients were aged between 18 and 80 years, had a confirmed diagnosis of diabetes with acceptable glycemic control, had been receiving established diabetic therapy for at least 3 months, and had a clinical diagnosis of distal symmetric sensory neuropathy with daily DPN-associated pain for the previous 3 months. On study entry, patient-rated diabetic pain had to be moderate or greater. Patients who met the inclusion criteria underwent a 2-week washout period during which all analgesics were discontinued, followed by 29 days of treatment with capsules containing DM 30 mg and Q 30 mg (DM30/Q30), beginning with 1 capsule/d and escalating at approximately 1-week intervals, as tolerated, to a maximum dose of 4 capsules/d (DM120/Q120). Tolerability was assessed based on adverse events and changes in clinical and laboratory parameters and nerve conduction velocity. Preliminary efficacy assessments included changes from baseline in scores on the pain intensity rating scale (PIRS), pain relief rating scale (PRRS), peripheral neuropathy quality-of-life instrument, and patients' diary assessments of sleep, present pain intensity, pain, and activity., Results: The study included 36 men and women (mean age, 58 years; mean body mass index, 32.8 kg/m(2)). Of the 33 subjects who completed the study, 23 (69.7%) did so at the highest permitted dose (DM120/Q120). The most commonly reported adverse events (occurring in > or =5% of subjects) were nausea (27.8%), dizziness (25.0%), and headache (25.0%). Three patients experienced 5 serious adverse events, only 1 of which was considered possibly related to study drug. The most commonly occurring laboratory abnormalities (involving glycosylated hemoglobin, serum glucose, triglycerides, and cholesterol) were considered typical of a population with diabetes. Improvements from baseline in scores on the PIRS, PRRS, and other exploratory efficacy measures were noted (P < 0.001)., Conclusions: The results of this open-label study indicated that the combination of DMIQ (dose range, DM30/Q30-DM120/Q120) was well tolerated in patients with pain associated with DPN. Based on the preliminary efficacy results, a randomized, controlled, double-blind trial is warranted to assess the tolerability and efficacy of this combination in patients with DPN.

BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal muscle under normal and resting conditions is in an inactive/phosphorylated state, which may contribute to muscle protein synthesis and muscle growth. Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA catabolism. Therefore, exercise may increase the BCAA requirement. It has been reported that BCAA supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. We have examined the effects of BCAA supplementation on delayed-onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in humans. The results obtained showed that BCAA supplementation prior to squat exercise decreased DOMS and muscle fatigue occurring for a few days after exercise. These findings suggest that BCAAs may be useful for muscle recovery following exercise.